Acyl derivatives of 1-amino-4-xanthenylpiperazine



United States Patent Ofifice ACYL DERIVATIVES F 1-AMINO-4- XANTHENYLPIPERAZINE John W. 'Cusic, Skokie, and Peter Yonan, Chicago, 111., assignors to G. D. Searle & Co., Chicago, Ill., a corporation of Delaware No Drawing. Filed May 18, 1966, Ser. No. 550,943 6 Claims. (Cl. 260268) The present invention relates to compounds which are hydrazides of N-aminopiperazines containing the Xanthene or thioxanthene structure. In particular, the present invention relates to compounds having the following general formula The halogen radicals referred to above include fluorine, chlorine, bromine, and iodine. The lower alkyl radicals as methyl, ethyl, propyl, is substituted phenyl, the substituents include methyl, halogen, methoxy, trifiuoromethyl, amino, and the like. Under these circumstances, R would be groups such as tolyl, fluorophenyl, chlorophenyl, methoxyphenyl, trifluoromethylphenyl, and aminophenyl.

The compounds of this invention are useful because of their pharmacological properties. In particular, they are useful as anti-ulcer agent-s; this activity is demonstrated by their inhibition of ulceration in the Shay rat. They also possess anti-inflammatory activity which is demonstrated by their phenylbutazone-like effect on edematous conditions. These activities of the present compounds are not accompanied by antibiotic activity.

The compounds of the present invention are conveniently prepared by the reaction of a 4-substituted l-aminopiperazine with an acylating agent. Thus, the appropriate acid halide, preferably the chloride, or an acid anhydride can be used in the acylation procedure. In addition, special acylating agents such as isatoic anhydride can be used to prepare the desired hydrazides of the present applicaton.

The following examples are presented to further il'ustrate the present invention; they shoud not be construed as limiting it in spirit or in scope. In these examples, quantities are indicated in parts by weight and temperature in degrees Centigrade C.).

Example I A solution of 4 parts of acetic anhydride in 30 parts of chloroform is added to a solution of 5 parts of l-arnino- 4-(9-xanthenyl)piperazine and parts of triethylamine in 120 parts of chloroform. The resultant mixture is refluxed with stirring for 2.5 hours and then cooled. The mixture is then washed with water and dried and the sol- 3,350,402 Patented Oct. 31, 1967 vent is evaporated under reduced pressure to leave a residual solid. This solid is recrystallized from a mixture of chloroform and ether to give 1-acetamido-4-(9-xanthenyl)pipel'azine melting at about 239241 C. This compound has the following formula If an equivalent quantity of propionic anhydride is substituted for the acetic anhydride and the above procedure is repeated, the product obtained is l-propionamido-4- 9-xanthenyl) piperazine.

Example 2 To a stirred suspension of 5 parts of 1-amino-4-(9-xanthenyl)piperazine mixture of chloroform and ether to give 1 cyclohexanecarboxamido 4 (9-xanthenyl)piperazine melting at about 220225 C.

Example 3 is added 10 1-benzamido-4-(9-xanthenyl)piperazine melting at about 258259 C. This compound has the following formula Example 4 Example 5 Other compounds which may be prepared according to the procedure of Example 3 by selecting the appropriate starting materials are, for example, 1-(3-trifluoromethylbenzamido)-4-(9-xanthenyl)piperazine melting at about 250-25 1 C., 1-(4-methylbenzamido)-4-(9-xan thenyl) piperazine, 1- (4-chlorobenzamido) -4- 9-xanthenyl)piperazine, l-(3-fluorobenzamido)-4-(9-xanthenyl)- 2. A compound according to claim 1 which has the piperazine, 1- (4-bromobenzamido -4- (9-xanthenyl piperformula azine, 1-(4-methoxybenzamido) 4 (9-xanthenyl)piperazine, l benzamido 4-(2-chloro-9-xanthenyl)piperazine, and 1-bcnzamido-4- (4-methyl-9-xanthenyl) piperazine. 5

What is claimed is: 1. A compound of the formula 10 3. A compound according to claim 1 which is 1-acetamido-4-(9-xanthenyl)piperazine. X 4. A compound according to claim 1 which is l-cyclohexanecarboxamido-4-(9-xanthenyl)piperazine.

5. A compound according to claim 1 which is l-benz- 15 amido-4-(9-Xanthenyl) piperazine.

6. A compound according to claim 1 which is 1-(3-trifluoromethylbenzamido) -4- 9-xanthenyl) piperazine.

wherein X selected from the group consisting of O and S; Y is selected from the group consisting of hydrogen, References Clted chlorine, and methyl; and R is selected from the group 20 UNITED STATES PATENTS Consisting of lower y cyclohexyl, p y y halo- 3,159,636 12/1964 Yonan et a1. 260-268 phenyl, methoxyphenyl, trifluoromethylphenyl, and aminophenyl. HENRY R. JILES, Primary Examiner.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,350,402 October 31, 1967 John W. Cusic et a1.

d that error appears in the above numbered pat- It is hereby certifie t the said Letters Patent should read as ent requiring correction and the corrected below.

lines 6 to 12, for that portion of the Column 2 "NH-CO-CO3" read -NHCOCH3 formula reading Signed and sealed this 25th day of February 1969.

(SEAL) Edward M. Fletcher, J r.

Commissioner of Patents Attesting Officer 

1. A COMPOUND OF THE FORMULA 